Inhibition of rotavirus replication by prostaglandin A: evidence for a block of virus maturation.

Rotaviruses are recognized as the leading cause of severe viral gastroenteritis in young children and in immunocompromised patients. Cyclopentenone prostaglandins possess antiviral activity against several single-strand RNA viruses; therefore, the effect of prostaglandin A1 (PGA1) on SA-11 simian rotavirus infection was investigated in cultured cells. PGA1 potently inhibited SA-11 rotavirus replication. Whereas it did not affect virus adsorption or penetration, PGA1 partially inhibited VP4 and VP7 synthesis and selectively reduced glucosamine incorporation into the NSP4 viral enterotoxin. Electron microscopy analysis showed that, despite normal formation of cytoplasmic inclusions and budding of particles into the rough endoplasmic reticulum, virus maturation was impaired in PGA1-treated cells, with most of the virus particles remaining in the membrane-enveloped intermediate form. Because prostaglandins are used clinically as cytoprotective drugs for gastric ulcers, these observations offer new perspectives in the search for therapeutic agents for rotavirus-induced gastroenteritis.